Surfactant protein-A suppresses eosinophil-mediated killing of Mycoplasma pneumoniae in allergic lungs.
Surfactant protein-A suppresses eosinophil-mediated killing of Mycoplasma pneumoniae in allergic lungs.
复制标题
DOI：
10.1371/journal.pone.0032436
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Wright JR
中科院分区：
文献类型：
--
作者：
Ledford JG;Mukherjee S;Kislan MM;Nugent JL;Hollingsworth JW;Wright JR
表面活性蛋白-A(SP-A)在减少细菌和病毒感染方面具有公认的功能，但其在哮喘等慢性肺部疾病中的作用尚不清楚。肺炎支原体(MP)经常在慢性哮喘患者的呼吸道中定植，并被认为是哮喘加重的原因之一。我们的实验室以前曾报道，在非过敏性呼吸道的MP感染过程中，SP-A通过抑制过度热情的肿瘤坏死因子-α介导的反应来帮助维持气道的动态平衡，在过敏性小鼠中，SP-A调节嗜酸性粒细胞的渗透和呼吸道的炎症。在本研究中，我们使用野生型(WT)和SP-A−/−过敏性小鼠的体内模型，用模式抗原OVA(OVA)同时感染MP(OVA+MP)来验证SP-A改善MP诱导的嗜酸性粒细胞刺激的假设。因此，SP-A可以保护过敏性呼吸道免受嗜酸性粒细胞炎症产物的释放所致的损伤。与相同治疗组的WT小鼠相比，SP-A缺陷小鼠在并发过敏性呼吸道疾病和感染(OVA+MP)期间的炎症细胞、粘液产生和肺损伤显著增加。相反，与WT小鼠相比，SP-A缺陷小鼠的MP负荷显著降低。与WT小鼠相比，嗜酸性粒细胞特异性因子--嗜酸性粒细胞过氧化物酶(EPO)在过敏/感染的SP-A−/−小鼠的样本中增强，该因子参与了病原体的杀死，也参与了由于常驻肺蛋白的氧化损伤而导致的上皮功能障碍。用纯化的嗜酸性粒细胞和人SP-A进行的体外实验表明，SP-A限制了MP刺激的嗜酸性粒细胞释放EPO，从而降低了它们的杀伤能力。这些发现首次证明，虽然SP-A通过介导MP与嗜酸性粒细胞的相互作用来干扰嗜酸性粒细胞介导的MP的生物清除，但SP-A同时通过限制炎症和损伤而有益于呼吸道。
Surfactant protein-A (SP-A) has well-established functions in reducing bacterial and viral infections but its role in chronic lung diseases such as asthma is unclear. Mycoplasma pneumoniae (Mp) frequently colonizes the airways of chronic asthmatics and is thought to contribute to exacerbations of asthma. Our lab has previously reported that during Mp infection of non-allergic airways, SP-A aides in maintaining airway homeostasis by inhibiting an overzealous TNF-alpha mediated response and, in allergic mice, SP-A regulates eosinophilic infiltration and inflammation of the airway. In the current study, we used an in vivo model with wild type (WT) and SP-A−/− allergic mice challenged with the model antigen ovalbumin (Ova) that were concurrently infected with Mp (Ova+Mp) to test the hypothesis that SP-A ameliorates Mp-induced stimulation of eosinophils. Thus, SP-A could protect allergic airways from injury due to release of eosinophil inflammatory products. SP-A deficient mice exhibit significant increases in inflammatory cells, mucus production and lung damage during concurrent allergic airway disease and infection (Ova+Mp) as compared to the WT mice of the same treatment group. In contrast, SP-A deficient mice have significantly decreased Mp burden compared to WT mice. The eosinophil specific factor, eosinophil peroxidase (EPO), which has been implicated in pathogen killing and also in epithelial dysfunction due to oxidative damage of resident lung proteins, is enhanced in samples from allergic/infected SP-A−/− mice as compared to WT mice. In vitro experiments using purified eosinophils and human SP-A suggest that SP-A limits the release of EPO from Mp-stimulated eosinophils thereby reducing their killing capacity. These findings are the first to demonstrate that although SP-A interferes with eosinophil-mediated biologic clearance of Mp by mediating the interaction of Mp with eosinophils, SP-A simultaneously benefits the airway by limiting inflammation and damage.
登录
查看更多内容
DOI：
10.1084/jem.185.5.885
发表时间：
1997-03-03
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Korsgren M;Erjefält JS;Korsgren O;Sundler F;Persson CG
通讯作者：
Persson CG
影响因子：
4.4
作者：
Ledford, Julie G.;Goto, Hisatsugu;Wright, Jo Rae
通讯作者：
Wright, Jo Rae
DOI：
10.1073/pnas.93.18.9594
发表时间：
1996-09-03
影响因子：
11.1
作者：
Korfhagen, TR;Bruno, MD;Whitsett, JA
通讯作者：
Whitsett, JA
影响因子：
4.4
作者：
Forbes, E;Murase, T;Hogan, SP
通讯作者：
Hogan, SP
影响因子：
64.5
作者：
Gardai, SJ;Xiao, YQ;Henson, PM
通讯作者：
Henson, PM